1. Field of the Invention
The present invention relates to emulsifying preparations which contain an oil-soluble active ingredient, which is superior in long-term preservation stability.
2. Discussion of the Background
Conventionally, a number of oil-soluble drugs as well as oil-soluble components such as oil-soluble vitamins, dyes, flavors, plant essential oils, and the like are known as active ingredients to be added to pharmaceutical products, foods and the like. These oil-soluble components can be dissolved in oil and provided in the form of a capsule. For wide utilization in pharmaceutical products such as liquid and the like, foods such as drinks and the like, the use of an aqueous phase system is desired to be enabled.
To contain an oil-soluble component in an aqueous phase, therefore, various solubilization, dispersion, and emulsification techniques have been considered. For example, there are: a technique in which ultrafine crystals of an oil-soluble dye are dispersed in a mixture of polyglycerol fatty acid ester having the below-mentioned HLB value of 10-15, sorbitan ester of fatty acid having an HLB value of 2-6 and/or diglycerol fatty acid ester having an HLB value of 2-6, polyols and water (see JP-A-2008-63476); a method in which a polyglycerol fatty acid monoester made of a polyglycerol having an average degree of polymerization of not less than 5 and myristic acid or oleic acid monoester, and polyol are mixed at a particular ratio and a homogeneous treatment is performed (see JP-A-H10-84887); a technique in which a polyglycerol fatty acid monoester made of polyglycerol having an average degree of polymerization of 6-10 and saturated fatty acid having a carbon number of 12-14, and fats and oils are mixed at a particular ratio to solubilize the fats and oils (see patent document 3: JP-A-H9-168369); and the like. In addition, a technique in which the pH of emulsifying preparations containing capsinoid compounds in chili pepper containing various physiologically active components is set to fall within a particular range has been disclosed (see JP-A-2003-192576).
The emulsifying preparations shown in the above-mentioned patent documents were those prepared by using a polyglycerol fatty acid ester produced by a conventional production method. In the polyglycerol fatty acid ester produced by a conventional production method here, the polyglycerol used as a starting material is generally obtained by dehydrative condensation of glycerol as a starting material in the presence of a catalyst such as sodium hydroxide and the like under heating, followed by purification as necessary by distillation, decoloration, deodorizing, ion exchange resin treatment, and the like.
The polyglycerol produced by such steps is a mixture of dehydratively-condensed compounds of glycerol having different structures. This is because the molecular structure of polyglycerol produced varies depending on which hydroxyl group is involved in the reaction during the condensation of glycerols, since glycerol has two primary hydroxyl groups and one secondary hydroxyl group. The structure of polyglycerol has a great influence on the properties of polyglycerol fatty acid ester. Conventional polyglycerol esters of fatty acid are not designed in consideration of the structure of a hydrophilic group to meet the use object, and therefore, the properties thereof are not sufficiently exhibited. Although the information reflecting the molecular structure of polyglycerol can be obtained by various methods, determination of a rigorous molecular structure is meaningless since it is a mixture as mentioned above. However, it is possible to increase the molecular species having a certain tendency by combining synthesis methods and purification methods, even if it is a mixture.
In general, with regard to polyglycerol, for example, decaglycerol refers to polyglycerol having a degree of polymerization of 10. However, those actually commercially available include many polyglycerols having a degree of polymerization of other than 10, and they are mixtures of polyglycerols having various degrees of polymerization. As a method of determining the average degree of polymerization of polyglycerol, an end-group analysis method is generally used, which determines by calculation from the relationship between a measurement value of hydroxyl value and a theoretical value thereof. Therefore, conventional polyglycerol is, even if it is a decaglycerol, characterized in that it contains decaglycerol having a degree of polymerization of 9 or 10 in a comparatively small amount, and instead, decaglycerol having a low degree of polymerization in a large amount, where the total of decaglycerol having a degree of polymerization of not less than 6 is less than 65 wt %, the total of decaglycerol having a degree of polymerization of not less than 7 is less than 60 wt %, and the total of decaglycerol having a degree of polymerization of not less than 8 is less than 50 wt %. Moreover, the total of polyglycerol produced by a conventional method and having a linear or branched chain structure is less than 60 wt %. The rest mostly has a cyclic structure. A conventional production method cannot determine which hydroxyl group reacts during condensation of glycerols, and also produces many cyclic polyglycerols. When compared to polyglycerol having a linear or branched chain structure, polyglycerol having a cyclic structure contains less hydroxyl group, which decreases hydrophilicity, and cannot maintain emulsification stability easily for a long time since the cyclic structure becomes an inhibitory factor for emulsification. Therefore, an ester of polyglycerol produced by a conventional production method and fatty acid cannot retain high emulsification performance and high solubilization performance and cannot maintain a stable emulsification state for a long time.
Examples of the surfactants for foods currently available on the market include sucrose esters of fatty acid, polyoxyethylene sorbitan fatty acid esters, and the like. When drinks containing a liposoluble vitamin such as vitamin E and the like, and an oil-soluble useful substance such as β-carotene and the like are produced using such surfactant having a high HLB value, a product that is stable for a long time cannot be produced. As a result, an auxiliary agent such as ethanol and the like needs to be added to achieve sufficient and stable emulsification performance. However, when such drinks are taken in a large amount, drunkenness occurs, sometimes causing a social problem particularly among young people. That is, by a technique using a conventional polyglycerol fatty acid ester, it is difficult to provide a stable emulsified state superior in sensory aspects such as taste, texture, and the like, since emulsification performance is insufficient. In addition, the polyoxyethylene sorbitan fatty acid esters and sucrose esters of fatty acid widely used as surfactants for foods show insufficient emulsification and solubilization performances, and cannot be sufficient substitutes.
Considering the application to pharmaceutical products and foods, moreover, it is preferable in terms of sensory aspects such as taste, texture, and the like to add higher amounts of oil-soluble components or oil phase components desired to be added to an emulsifying preparation and to decrease the amount of the emulsifying preparation itself to be added to pharmaceutical products such as liquid and the like and foods such as drinks and the like, since the amounts of a solubilizer, a dispersing agent, and an emulsifier to be ingested become small. When an emulsifying preparation is applied to liquid pharmaceutical products such as liquids and the like or liquid foods such as drinks and the like, it is necessary to maintain a stable, solubilized, dispersion or emulsified state for a long time without creaming, oil phase separation, and the like. For this end, it is desirable to maintain a good emulsified state during the use period or best-before period of the emulsifying preparation.